Hormone Replacement Study Answers Questions, but Not All

By JANE E. BRODY

Published: January 18, 1995

THE recently reported finding that various forms of hormone replacement therapy can lower the risk of heart disease in postmenopausal women has answered many concerns about the safety and effectiveness of taking estrogen and progesterone in middle age, but it has also raised important new questions, according to Dr. Bernadine Healy, former director of the National Institutes of Health.

In an editorial in today's issue of The Journal of the American Medical Association, in which details of the study are also published, Dr. Healy wrote that "after a half century of conflicting data, we can affirm with growing confidence that, at the very least, estrogen reduces key cardiovascular risk factors in women at a time when they become especially vulnerable to heart disease, namely, after 50 years of age."

Furthermore, she noted that the study showed that when progesterone was added to the formula, to prevent uterine cancer, the estrogen benefits to the heart were not lost. The study's findings were first reported in November at the annual meeting of the American Heart Association.

Previous studies had found that in postmenopausal women who still have a uterus, supplementary estrogen, if taken alone, resulted in a ninefold increase in the risk of developing cancer of the endometrium, the lining of the uterus. Gynecologists now recommend that progesterone be included in hormone replacement therapy, but it was feared that this addition would negate the estrogen's benefits to the heart.

The new study confirmed that estrogen alone is hazardous to the uterus, although it is still the preferable postmenopausal therapy for a woman whose uterus has been removed by hysterectomy, because it has the most beneficial effect on cardiovascular risk.

This most carefully designed study of hormone replacement was conducted over a three-year period at seven clinical centers among 875 healthy women from 45 to 64 years old. It showed that all the tested regimens, with or without progesterone, reduced women's cardiovascular risks. The greatest benefit to the heart, after estrogen taken alone, was observed when a little-known form of natural progesterone, called micronized progesterone, was administered for 12 days of each month along with daily low-dose estrogen.

A slightly less striking benefit was seen when low doses of estrogen (Premarin) and a synthetic progesterone, medroxyprogesterone acetate (Provera), were given daily. The study was sponsored by the National Institutes of Health.

Contrary to "a recurrent concern," Dr. Healy said, the new study showed that hormone replacement therapy did not raise blood pressure or increase the blood's tendency to form clots that could precipitate a stroke or heart attack. Nor do the hormone replacement regimens tested have adverse effects on how the body processes sugar.

But Dr. Healy added, "As important as this trial is, it is still only a start in answering the pressing questions about hormone replacement therapy and its many formulations." As the researchers themselves pointed out, it has yet to be shown that the improvements in cardiovascular risk factors associated with hormone therapy will translate into fewer heart attacks and strokes. The study examined the benefits and risks of hormone replacement therapy for only three years, and a longer-term study now under way by the Women's Health Initiative of the National Institutes of Health will not answer this question for at least five years.

Heart disease is by far the leading killer of American women. Dr. Healy said previous "observational studies" had suggested that hormone therapy could reduce the risk of coronary death by as much as 50 percent, a benefit that would more than outweigh the increase in cancer risk associated with taking the hormones.

Although the current study found no hint of an increase in breast cancer, the researchers said three years was not long enough to assess such a risk. Nonetheless, they noted that even if there were some risk of hormone therapy to the breast, the potential benefits to the heart would probably far outweigh it.

Other matters requiring further study, Dr. Healy wrote, include the possibility that hormone therapy can help prevent strokes and osteoporosis, as well whether it might play a role in depression, Alzheimer's disease and other cancers.

Dr. Healy, who is now at the Page Center for Health and Science Policy Studies at the Cleveland Clinic Foundation, said it was not yet known how long a woman should get hormone therapy to reap the maximum benefits and the lowest risks. Nor has it been established whether administering hormone therapy through a skin patch will be as effective as taking the hormones by mouth.